# EUR-Lex - 52013PC0472 - EN

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# 52013PC0472

**Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL on fees payable to the European Medicines Agency for the conduct of pharmacovigilance activities in respect of medicinal products for human use /* COM/2013/0472 final - 2013/0222 (COD) */**

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EXPLANATORY MEMORANDUM

1.           CONTEXT OF THE PROPOSAL

The legal framework of pharmacovigilance
for medicinal products for human use marketed within the EU is provided for in
Regulation (EC) No 726/2004[1]
('the Regulation') and in Directive 2001/83/EC[2]
('the Directive'). The EU pharmacovigilance legislation for medicinal products
for human use has been subject to a major review and an impact assessment that
led to the adoption of a revised legislation[3]
in 2010, which strengthens and rationalises the system for safety monitoring of
medicines on the European market. This legislation is applicable as of July
2012. It provides for a number of EU-wide procedures to assess
pharmacovigilance data which may lead to regulatory action. Some additional
amendments to the pharmacovigilance legislation were introduced in 2012
following the 'Mediator' case[4].

Whilst streamlining the EU-wide
post-authorisation safety assessment and monitoring of medicines, the revised
pharmacovigilance legislation significantly widened the tasks of the European
Medicines Agency ('the Agency') with regard to pharmacovigilance, irrespective
of whether the medicinal products have been authorised via the 'centralised
procedure' (in accordance with the Regulation) or via national procedures (in
accordance with the Directive). The Agency has therefore acquired
pharmacovigilance competences also for nationally authorised medicines, in
addition to reinforced competences for centrally authorised medicines.

To finance these activities, the revised pharmacovigilance
legislation provides for fees to be charged to marketing authorisation holders.
These fees should be related to pharmacovigilance activities performed at the
level of the EU, notably in the context of the EU-wide assessment procedures.
These procedures include scientific assessment carried out by rapporteurs from the
national competent authorities of the Member States. These fees are therefore
not intended to cover the pharmacovigilance activities of the national
competent authorities performed at national level. Member States may
accordingly continue to charge fees for the activities performed at national
level which should, however, not overlap with the fees laid down in this legal
proposal.

Since the revised pharmacovigilance
legislation only concerns medicinal products for human use, this proposal on
fees for pharmacovigilance only covers these medicinal products.

2.           RESULTS OF CONSULTATIONS WITH THE
INTERESTED PARTIES AND IMPACT ASSESSMENTS

Public Consultation

As part of the preparation of this legal
proposal on fees for pharmacovigilance, DG SANCO, in close collaboration with
the Agency, drafted a concept paper for public consultation. Given that the
Union-wide pharmacovigilance procedures foreseen in the revised
pharmacovigilance legislation are new procedures, the concept paper used
existing procedures that were considered sufficiently similar as benchmarks for
the new procedures. In addition, a pharmacovigilance service fee to be charged
on an annual basis was considered in the paper, in order to cover those
activities of the Agency that benefit industry in general, but for which it is virtually
impossible to identify the individual addressee(s).

The Commission launched the public
consultation on 18 June 2012 with a deadline for replies on 15 September 2012.
In total, 85 replies were received (mainly from industry, but also from the Member States and other stakeholders). The summary of the replies to the public consultation
was published on the website of DG SANCO on 29 November 2012. In general, the
comments were rather negative, notably as regards the amounts proposed for the
fees. They were considered to be too high and without sufficient justification
as regards the workload and costs. Grouping of marketing authorisation holders,
especially for submitting a single Periodic Safety Update Report, was
considered by many as not applicable in practice. Many respondents questioned
the benchmarks that were used and considered that pharmacovigilance fees should
be rather based on estimations of the time spent and the associated cost of the
assessment work. Several industry respondents flagged the risk of possible double
charging of the Agency and the Member States, given that many of the competent
authorities in the Member States currently charge fees for pharmacovigilance.
Particular concerns were expressed by small and medium-sized enterprises,
stating that despite the proposed fee reductions in the concept paper, the
amounts were still too high. Also many responses from industry associations,
representing products such as generic medicinal products, considered that the
proposed fee levels would unfairly affect marketing authorisation holders with
a large portfolio of products with well-established safety profiles.

Impact assessment

In line with the above-mentioned comments,
the Impact Assessment report that accompanies this proposal considered several
options, based on estimation of cost. This new approach is in line with the
recommendations of the European Court of Auditors[5] and the European Parliament[6] to base the payment system for
services provided by Member States' authorities on costs.

Consistent with the legal proposal on
pharmacovigilance of 2008 and with the EU legislation on pharmacovigilance, all
options of legislative action were based on the assumption that the total cost
related to pharmacovigilance would be covered through fees. Regulation (EU) No
1235/2010 provides notably for a new wording of article 67(3) of Regulation
(EC) No 726/2004: 'The Agency’s revenue shall consist of a contribution from
the Union and fees paid by undertakings for obtaining and maintaining Union
marketing authorisations and for other services provided by the Agency, or by
the coordination group as regards the fulfilment of its tasks in accordance
with Articles 107c, 107e, 107g, 107k and 107q of Directive 2001/83/EC.’ Recital
13 notably states that 'It should be ensured that adequate funding is possible
for pharmacovigilance activities by empowering the Agency to charge fees to
marketing authorisation holders. ' and Recital 24 explains that the new legal
provisions 'widen the tasks of the Agency with regard to pharmacovigilance,
including the monitoring of literature cases, the improved use of information
technology tools and the provision of more information to the general public.
The Agency should be enabled to fund these activities from fees charged to
marketing authorisation holders.'

The selected option foresees two separate types
of fees:

(1)          Fees for procedures for
the assessment of periodic safety update reports, post-authorisation safety
studies and pharmacovigilance referrals.

(2)          An annual flat fee to be
charged to marketing authorisation holders having at least one medicinal
product that is authorised in the EU and registered in the database provided for
in Article 57(1)(l) of the Regulation. This annual flat fee would cover only
the costs of the pharmacovigilance activities of the Agency other than those
related to the above-mentioned procedures. Therefore, it is foreseen that the
fee revenue from the annual flat fee be retained by the Agency.

Some fee reductions and fee waivers are
foreseen in respect of the proposed fees:

· In line with the general EU policy to support small and medium-sized
enterprises, reductions for medicinal products for which the marketing
authorisation holder is a small or medium-sized enterprise would be granted for
all types of fees. Micro enterprises would be exempted from all fees. The
reduction rates for small and medium-sized enterprises are based on the
comparisons of data of added values per employee in the sector, as a possible
measure of profitability of companies. The proposed contribution of small and
medium enterprises to the financing of pharmacovigilance was reduced
accordingly, whereas micro-enterprises should be entirely exempt from the
obligation to pay pharmacovigilance fees.

· Moreover, certain fee reductions reflect the risk-based approach of
the pharmacovigilance legislation acknowledging the differences in the safety
profile of new and more established medicinal products for which time has
allowed to collect data. A reduction of the annual flat fee is therefore proposed
for authorised generic, homeopathic and herbal medicinal products and for
medicinal products authorised on grounds of well-established medical use. However,
where these medicinal products are included in the Union-wide pharmacovigilance
procedures, the full fees for procedures would apply. Registered homeopathic
and herbal medicinal products would be exempted from all fees.

· Finally, as marketing authorisation holders for medicinal products
authorised under the Regulation currently pay an annual fee to the Agency for
maintenance of the authorisation including pharmacovigilance activities covered
by the proposed fee, these marketing authorisations would be exempted from the
annual flat fee in order to avoid double charging.

Marketing authorisation holders would be
charged as follows:

· Marketing authorisation holders having at least one product involved
in a Union-wide pharmacovigilance procedure would be charged a fee for procedures,

· Marketing authorisation holders in the EU[7], with the exceptions explained
above, would be charged the annual flat fee.

Therefore, marketing authorisation holders
that are not involved in any EU procedure would only pay the annual flat fee
component, with the above-mentioned exceptions.

The criteria that were identified as the
most decisive in analysing the impact of options were fairness, proportionality
and transparency of the overall pharmacovigilance fee system, including the
adequacy of the relation between the work carried out and the type and level of
fee. Other important criteria considered within the analysis were the stability
and the simplicity of the Agency pharmacovigilance fee-system.

Under the selected option, fees are
proportionate to the workload and the costs, but cannot be entirely predictable
by the inherent nature of the pharmacovigilance activities. In order to avoid
extreme cases and to allow for a readable, applicable and usable legislative
text, it is proposed that procedure-based fees generate an average fee revenue
that is based on the average estimated cost of each procedure.

A combination of procedure-based fees and an
annual flat fee has been considered to be the most transparent, cost-based, activity-based
and proportionate way of setting the new fees, in order to cover the cost under
the new pharmacovigilance legislation. This analysis was carried out in the
light of a strong preference expressed by stakeholders for a policy approach
based on fairness and transparency. With this approach, the products being part
of a pharmacovigilance procedure at EU level will contribute to the financing
of the cost of the procedure. This is also in line with the risk-based approach
of the pharmacovigilance legislation. At the same time, the cost of general
pharmacovigilance activities of the Agency, and only that part of its total
pharmacovigilance cost, would be recouped through the annual flat fee charged to
marketing authorisation holders who benefit overall from the EU
pharmacovigilance system. These activities of the Agency relate notably to the
information technology systems, safety data management and literature
monitoring.

In order to have a fair system, it was
considered necessary to identify a single, chargeable unit as there are
different ways in the EU of assigning authorisation numbers to and counting medicinal
products. To facilitate adverse reaction reporting and signal detection, it is
necessary to describe medicinal products with maximum precision in order to
take account of differences in strength, pharmaceutical forms, routes of
administration etc. Therefore, the Agency has set up the structure of the
database described in Article 57(2) of the Regulation to neutralise these
differences by means of individual entries. These entries have been chosen as a
chargeable unit.

Remuneration of Member States
authorities acting as rapporteurs

In line with the above-mentioned
recommendations of the European Court of Auditors and the European Parliament, it
is proposed that rapporteurs from the national competent authorities of the
Member States be remunerated according to a fixed scale based on estimations of
cost. The amount of remuneration is based on the average procedure costs as
estimated for each type of procedure. Where fee reductions apply, the
remuneration of the Member States will be adjusted accordingly, including
reductions for small and medium-sized enterprises which are in line with the
policy of the Union to support small and medium-sized enterprises.

3.           LEGAL
ELEMENTS OF THE PROPOSAL

Subsidiarity principle

The Agency is a European decentralised Agency
established under the Regulation and hence the decision on its funding and
charging of fees is to be taken at the EU level. The new pharmacovigilance
legislation provides a legal base for the Agency to charge fees for
pharmacovigilance. Hence, only the Union can act to enable the Agency to charge
fees for pharmacovigilance.

Only pharmacovigilance activities that are
performed at EU level and involving the Agency are covered by this proposal. As
regards pharmacovigilance activities remaining at national level, the EU is not
competent and Member States may still continue charging national fees
accordingly.

Proportionality principle

The proposal does not go beyond what is
necessary to achieve the general objective pursued, i.e. to introduce fees in
order to allow the proper implementation of the pharmacovigilance legislation
that is applicable since July 2012.

Legal basis

The proposed Regulation is, like the EU
pharmacovigilance legislation based on a dual legal basis: Article 114 and
Article 168(4)(c) TFEU. The proposed Regulation is based on Article 114 TFEU as
differences between national legislative, regulatory and administrative
provisions on medicinal products tend to hinder intra-Union trade and therefore
directly affect the operation of the internal market. This Regulation ensures
the availability of the necessary financial resources to apply the stream-lined
Union procedures for the assessment of serious safety issues for nationally
authorised products, which have been introduced amongst other things to prevent
or eliminate obstacles that could result from parallel procedures at national
level. Thereby this Regulation contributes to the well-functioning of the
internal market and the common post-marketing surveillance of medicinal
products.

In addition, the proposed Regulation is
based on Article 168(4)(c) TFEU as it aims at supporting the goal of setting
high standards of quality and safety of medicinal products. According to
Articles 168(4) and 4(2)(k) TFEU this Union competence is – like Article 114
TFEU - a shared competence which is exercised with the adoption of the proposed
Regulation.

The proposed Regulation aims at setting
high standards of quality and safety for medicinal products as it ensures the
availability of sufficient financial resources to perform the pharmacovigilance
activities that are necessary to guarantee that high standards are maintained
once the product is authorised.

Article 168(4)(c) TFEU cannot serve as sole
legal basis, but needs to be complemented with the legal basis of Article 114
TFEU as it, as set out above, pursues equally as object the establishment and
functioning of the internal market, and the setting of high standards of
quality and safety for medicinal products.

Choice of the legal instrument

Since the Treaty on the Functioning of the
European Union became applicable, all legislative procedures are normally based
on the previous 'co-decision procedure' involving both the Council and the
European Parliament. Therefore, for legal certainty, it is proposed to create
for pharmacovigilance fees a new Regulation of the Council and the European
Parliament, which will be subject to the ordinary legislative procedure (Article
294 of the TFEU).

The adoption of a proposal for a Regulation
on pharmacovigilance fees is aimed at allowing the Agency to have adequate
funding in order to properly implement the already applicable pharmacovigilance
legislation.

The existing Council Regulation (EC) No
297/95[8]
of 10 February 1995 on fees payable to the Agency would continue to apply,
whereas the proposed Regulation would apply to pharmacovigilance fees for
activities laid down in the applicable pharmacovigilance legislation. The two
legal instruments would be complementary.

4.           BUDGETARY IMPLICATION

Consistent with the legal proposal on
pharmacovigilance of 2008 and with the Pharmacovigilance legislation adopted in
2010, according to which the Agency should be enabled to fund pharmacovigilance
activities from fees charged to marketing authorisation holders (see section on
Impact Assessment), all options of legislative action, including the option
which underpins this proposal, were based on the assumption that the costs
related to pharmacovigilance would be covered through fees.

Therefore, no impact on the EU general
budget is foreseen in the accompanying financial statement of this proposal.

5.           OPTIONAL ELEMENTS

European Economic Area

The
proposed act is of relevance to the EEA.

2013/0222 (COD)

Proposal for a

REGULATION OF THE EUROPEAN PARLIAMENT
AND OF THE COUNCIL

on fees payable to the European Medicines
Agency for the conduct of pharmacovigilance activities in respect of medicinal
products for human use

(Text with EEA relevance)

THE EUROPEAN PARLIAMENT AND THE
COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty on the
Functioning of the European Union, and in particular Article 114 and Article
168(4)(c) thereof

Having regard to the proposal from the
European Commission,

After transmission of the draft legislative
act to the national Parliaments,

Having regard to the opinion of the
European Economic and Social Committee[9],

Having regard to the opinion of the
Committee of the Regions[10],

Acting in accordance with the ordinary legislative
procedure,

Whereas:

(1)       The revenues of the European
Medicines Agency (hereinafter ‘the Agency’) consist of a contribution from the
Union and fees paid by undertakings for obtaining and maintaining Union
marketing authorisations and for other services referred to in Article 67(3) of
Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31
March 2004 laying down Community procedures for the authorisation and
supervision of medicinal products for human and veterinary use and establishing
a European Medicines Agency[11].

(2)       The provisions on pharmacovigilance
relating to medicinal products of human use laid down in Regulation (EC) No
726/2004 and Directive 2001/83/EC of the European Parliament and of the Council
of 6 November 2001 on the Community code relating to medicinal products for
human use[12]
were amended by Directive 2010/84/EU of the European Parliament and of the
Council of 15 December 2010 amending, as regards pharmacovigilance,
Directive 2001/83/EC on the Community code relating to medicinal products for
human use[13],
Regulation (EU) No 1235/2010 of the European Parliament and of the Council of
15 December 2010 amending, as regards pharmacovigilance of medicinal
products for human use, Regulation (EC) No 726/2004 laying down Community
procedures for the authorisation and supervision of medicinal products for
human and veterinary use and establishing a European Medicines Agency, and
Regulation (EC) No 1394/2007 on advanced therapy medicinal products[14], Directive 2012/26/EU of the
European Parliament and of the Council of 25 October 2012 amending
Directive 2001/83/EC as regards pharmacovigilance[15] and Regulation (EU) No 1027/2012
of the European Parliament and of the Council of 25 October 2012 amending
Regulation (EC) No 726/2004 as regards pharmacovigilance[16]. Those amendments only cover medicinal
products for human use. Those amendments provide for new pharmacovigilance tasks
for the Agency including Union-wide pharmacovigilance procedures, the
monitoring of literature cases, the improved information technology tools and
the provision of more information to the general public. Furthermore, the
pharmacovigilance legislation stipulates that the Agency should be enabled to
fund those activities from fees charged to marketing authorisation holders. New
categories of fees should therefore be created to cover the new and specific
tasks of the Agency.

(3)       In order to enable the
Agency to charge fees for those new pharmacovigilance tasks, a Regulation
should be adopted. The fees provided for in this Regulation should be
applicable without prejudice to the fees laid down in Council Regulation (EC)
No 297/95 of 10 February 1995 on fees payable to the Agency [17]as that Regulation covers fees
for activities of the Agency in respect of medicinal products authorised under
Regulation (EC) No 726/2004.

(4)       This Regulation should be
based on the double legal basis of Article 114 and Article 168(4)(c) of the Treaty
on the Functioning of the European Union (TFEU). It aims at financing
pharmacovigilance activities that contribute to achieving an internal market as
regards medicinal products for human use, taking as a base a high level of
protection of health. At the same time, the Regulation provides financial
resources supporting the activities to address common safety concerns in order
to maintain high standards of quality, safety and efficacy of medicinal
products for human use. Both objectives are being pursued simultaneously and
are inseparably linked, so that one is not secondary to another.

(5)       The structure and amounts
of the fees for pharmacovigilance collected by the Agency as well as the rules
for payment should be established. The structure of the fees should be as simple
as possible to apply in order to minimise the related administrative burden.

(6)       In
line with the Joint Statement of
the European Parliament, the Council of the EU and the European Commission of 19
July 2012 on the Common Approach on decentralised agencies, for bodies for
which the revenue is constituted by fees and charges in addition to the Union
contribution, fees should be set at a level such as to avoid a deficit or a
significant accumulation of surplus and be revised when this is not the case. Therefore, the fees set out in this Regulation should be based on
an evaluation of the Agency’s estimations and forecasts as regards its workload
and related costs and on the basis of an evaluation of the costs of the work
carried out by the competent authorities of the Member States acting as
rapporteurs in accordance with Articles 61(6), 62(1) of Regulation (EC) No
726/2004 and Articles 107e 107q and 107j of Directive 2001/83/EC.

(7)       Fees referred to in this
Regulation should be transparent, fair and proportionate to the work carried
out.

(8)       This Regulation should only
refer to fees which are to be levied by the Agency, whereas the competence to
decide on possible fees levied by the competent authorities of the Member
States should remain with the Member States. Marketing authorisation
holders should not be charged twice for the same pharmacovigilance activity. Member
States should therefore not levy fees for the activities which are covered by
this Regulation.

(9)       For reasons of
predictability and clarity, the amounts of the fees should be established in
euro.

(10)     Two different types of fees
should be levied under this Regulation in order to take account of the
diversity of tasks of the Agency and of the rapporteurs. Firstly, fees for the
pharmacovigilance procedures carried out at Union level should be charged to
those marketing authorisation holders whose medicinal products are part of the
procedure. Those procedures relate to the assessment of periodic safety update
reports, assessment of post-authorisation safety studies and assessments in the
context of referrals initiated as a result of pharmacovigilance data. Secondly,
an annual flat fee should be charged for other pharmacovigilance activities
carried out by the Agency that benefit marketing authorisation holders overall.
Those activities relate to information technology, notably maintenance of the
'Eudravigilance' database referred to in Article 24 of Regulation (EC) No
726/2004, signal detection and monitoring of selected medical literature.

(11)     Marketing authorisation
holders for medicinal products authorised under Regulation (EC) No 726/2004
already pay an annual fee to the Agency for the maintenance of their
authorisations, which includes pharmacovigilance activities that are covered by
the annual flat fee established by this Regulation. In order to avoid double charging
for those pharmacovigilance activities of the Agency, the annual flat fee
established by this Regulation should not be charged for marketing
authorisations granted under Regulation (EC) No 726/2004.

(12)     The work carried out at Union
level in respect of the assessment of non-interventional post-authorisation
safety studies imposed by an authority and of which the protocol has been
endorsed by the Pharmacovigilance Risk Assessment Committee, involves the
supervision of these studies, starting from the assessment of the draft
protocol, and is not limited to the assessment of the final study reports. Therefore,
the fee levied for this procedure in respect of studies that have been
finalised should cover all the work relating to the study. In order to avoid
double charging, marketing authorisation holders who are charged the fee for the
assessment of non-interventional post-authorisation safety studies imposed by
an authority, should be exempted from any other fee charged by a competent
authority for the submission of those studies.

(13)     Rapporteurs rely for their
assessment on the scientific evaluation and resources of national marketing
authorisation bodies, whilst it is the responsibility of the Agency to coordinate
the existing scientific resources put at its disposal by the Member States. In
view of that and to ensure adequate resources for the scientific assessments
relating to the Union-wide pharmacovigilance procedures, the Agency should
remunerate the scientific assessment services provided by the rapporteurs appointed
by Member States as members of the Pharmacovigilance Risk Assessment Committee referred
to in Article 56(1)(aa) of Regulation (EC) No 726/2004 or, where relevant, by
rapporteurs in the coordination group referred to in Article 27 of Directive 2001/83/EC.
The level of remuneration for the work carried out by those rapporteurs should
be based on average estimations of the workload involved and should be taken
into account in setting the level of the fees for Union-wide pharmacovigilance
procedures.

(14)     Fees should be levied on a
fair basis on all marketing authorisation holders. Therefore, a single
chargeable unit should be established irrespective of the procedure under which
the medicinal product has been authorised, either under Regulation (EC) No 726/2004
or under Directive 2001/83/EC and the way in which authorisation numbers are
assigned by the Member States. The individual entries corresponding to authorisations in the database referred to in Article
57(1)(l) of Regulation (EC) No 726/2004 based on information from the
list of all medicinal products for human use authorised in the Union referred
to in Article 57(2) thereof meet this
objective.

(15)     In line with the policy of
the Union to support small and medium-sized enterprises, reduced fees should
apply to small and medium-sized enterprises within the meaning of Commission
Recommendation 2003/361/EC of 6 May 2003 concerning the definition of micro,
small and medium-sized enterprises[18].
Consistent with this policy, micro enterprises within the meaning of that
Recommendation should be exempted from all fees under this Regulation.

(16)     Generic medicinal products,
medicinal products authorised under the provisions relating to well-established
medicinal use, authorised homeopathic medicinal products and authorised herbal
medicinal products should be subject to a reduced annual flat fee as those
products generally have a well-established safety profile. However, in cases
where these products are part of any of the Union-wide pharmacovigilance procedures,
the full fee should be charged in view of the work involved. As the legislation
on pharmacovigilance encourages the conduct of joint post authorisation safety
studies, marketing authorisation holders should share the applicable fee in case
a joint study is submitted.

(17)     Homeopathic and herbal
medicinal products registered in accordance with Article 14 and Article 16a of
Directive 2001/83/EC should be excluded from this Regulation as the pharmacovigilance
activities for these products are carried out by the Member States.

(18)     In order to avoid
disproportionate administrative workload for the Agency, reductions and
exemptions provided for in this Regulation should apply on the basis of a
declaration of the marketing authorisation holder that claims to be entitled to
the reduction or the exemption. The submission of incorrect information should
therefore be discouraged through an increase of the applicable amount of the
fee.

(19)     For reasons of consistency,
deadlines for the payment of fees levied under this Regulation should be established
taking due account of the deadlines of the procedures relating to
pharmacovigilance provided for in Regulation (EC) No 726/2004 and Directive
2001/83/EC.

(20)     Fees provided for under
this Regulation should be adapted when appropriate to take account of inflation
and, for that purpose, the European Index of Consumer Prices published by
Eurostat pursuant to Council Regulation (EC) No 2494/95 of 23 October 1995
concerning harmonised indices of consumer prices[19] should be used.

(21)     In order to allow for a sustainable
operation of the pharmacovigilance activities of the Agency and an appropriate
balance between the fee revenue and the underlying costs, the power to adopt
acts in accordance with Article 290 of the Treaty on the Functioning of the
European Union should be delegated to the Commission in respect of amendments to
the amounts, the reductions, the methods of calculation and the performance
information laid down in the Annex to this Regulation, notably through monitoring
the inflation rate in the EU and in light of the experience acquired with the
actual application of this Regulation. It is of particular importance that the
Commission carry out appropriate consultations during its preparatory work,
including at expert level. The Commission, when preparing and drawing up
delegated acts, should ensure a simultaneous, timely and appropriate
transmission of relevant documents to the European Parliament and to the
Council.

(22)     Since the objective of this
Regulation, namely to ensure adequate funding of pharmacovigilance activities
carried out at the level of the Union, cannot sufficiently be achieved by the
Member States and can, by reason of the scale of the measure, be better
achieved at Union level, the Union may adopt measures, in accordance with the
principle of subsidiarity as set out in Article 5 of the Treaty on European
Union. In accordance with the principle of proportionality, as set out in that
Article, this Regulation does not go beyond what is necessary in order to
achieve that objective.
For reasons of predictability, legal certainty and proportionality, the annual
flat fee should be levied for the first time by 31 January or by 1 July,
depending on the date of entry into force of this Regulation. The fees for union-wide
pharmacovigilance procedures should be levied for the first time after a reasonable
time period, following the entry into force of this Regulation, has elapsed.

HAVE ADOPTED THIS REGULATION:

Article 1

Subject
matter and scope

1.           This Regulation shall
apply to fees for pharmacovigilance activities relating to medicinal products
for human use authorised in the Union under Regulation (EC) No 726/2004 and
Directive 2001/83/EC which shall be levied by the European Medicines Agency
(hereinafter the ‘Agency’) on marketing authorisation holders.

2.           This Regulation determines
the activities performed at Union level for which fees are due, the amounts and
the rules of payment of those fees and the level of remuneration of the
rapporteurs.

3.           Micro enterprises within the
meaning of Recommendation 2003/361/EC shall be exempted from any fee under this
Regulation.

4.           The fees provided for in
this Regulation shall apply without prejudice to the fees laid down in Council
Regulation (EC) No 297/95[20].

Article 2

Definitions

For the purposes of this Regulation the
following definitions shall apply:

1.           'Chargeable unit' means each
individual entry in the database referred to in Article 57(1)(l) of Regulation
(EC) No 726/2004 based on information from the list of all medicinal products
for human use authorised in the Union referred to in Article 57(2) thereof.

2.           ‘Medium enterprise’ means a medium-sized enterprise
within the meaning of Recommendation 2003/361/EC;

3.           ‘Small enterprise’ means a small enterprise within the
meaning of Recommendation 2003/361/EC;

4.           ‘Micro enterprise’ means
a micro enterprise within the meaning of Recommendation 2003/361/EC.

Article 3

Types
of fees

1.           The fees for pharmacovigilance
activities shall consist of the following:

(a)
fees for Union-wide procedures as provided for
in Articles 4, 5 and 6 (hereinafter 'fees for procedures');

(b)
an annual flat fee as provided for in Article 7.

2.           Where a fee is levied by
the Agency in accordance with paragraph 1(a), the Agency shall remunerate the rapporteur
in the Pharmacovigilance Risk Assessment Committee appointed by the Member
State or the rapporteur in the coordination group (hereinafter 'the
rapporteur') for the work they carry out for the Agency or the coordination
group. This remuneration shall be paid in accordance with Article 9.

Article 4

Fee
for assessment of periodic safety update reports

1.           The Agency shall levy a fee
for the assessment of periodic safety update reports referred to in 107e and
107g of Directive 2001/83/EC and in Article 28 of Regulation (EC) No 726/2004.

2.           The amount of the fee is laid
down in Part I of the Annex.

3.           Where only one marketing
authorisation holder is subject to the obligation to submit a periodic safety
update report in the context of the procedures referred to in paragraph 1, the
Agency shall levy the total amount of the applicable fee on that marketing
authorisation holder.

4.           Where two or more
marketing authorisation holders submit periodic safety update reports in the
context of the procedures referred to in paragraph 1, the Agency shall divide the
total amount of the fee among those marketing authorisation holders in
accordance with Part I of the Annex.

5.           Where the marketing
authorisation holder referred to in paragraphs 3 and 4 is a small or medium-sized
enterprise, the amount payable by the marketing authorisation holder shall be
reduced as laid down in Part I of the Annex.

6.           The Agency shall levy the
fee under this Article by issuing a separate invoice to each marketing authorisation
holder concerned within thirty calendar days from the submission date of the
periodic safety update report established in accordance with Article 107c(4) of
Directive 2001/83/EC. Fees due under this Article shall be paid to the Agency within
thirty calendar days from the date on which the invoice is received by the
marketing authorisation holder.

Article 5

Fee
for assessment of post-authorisation safety studies

1.           The Agency shall levy a
fee for post-authorisation safety studies referred to in Article 21a(b) or
Article 22a(1)(a) of Directive 2001/83/EC and Article 9(4)(cb) or Article
10a(1)(a) of Regulation (EC) No 726/2004 for the assessment thereof carried out
under Articles 107n to 107q of Directive 2001/83/EC and Article 28b of
Regulation (EC) No 726/2004.

2.           The amount of the fee is
laid down in Part II of the Annex.

3.           Where the obligation to
conduct a post-authorisation safety study referred to in paragraph 1 is imposed
on more than one marketing authorisation holders, the same concerns applying to
more than one medicinal products, and where the marketing authorisation holders
concerned conduct a joint post-authorisation safety study, the amount payable
by each marketing authorisation holder shall be levied as laid down in Part II
section 3 of the Annex.

4.           Where the obligation to
conduct a post-authorisation safety study is imposed on a marketing authorisation
holder which is a small or medium-sized enterprise, the amount payable by the
marketing authorisation holder shall be reduced, as laid down in Part II of the
Annex.

5.           The Agency shall levy the
fee under this Article by issuing an invoice to each marketing authorisation
holder within thirty calendar days from the receipt of the final study report
by the Pharmacovigilance Risk Assessment Committee. Fees due under this Article
shall be paid within thirty calendar days from the date on which the invoice is
received by the marketing authorisation holder.

6.           Marketing authorisation
holders who are charged the fee under this Article shall be exempted from any
other fee charged by a competent authority for the submission of studies
referred to in paragraph 1.

Article 6

Fee
for assessments in the context of referrals initiated as a result of
the evaluation of pharmacovigilance data

1.           The Agency shall levy a
fee for the assessment carried out in the context of a procedure initiated as a
result of the evaluation of pharmacovigilance data under Articles 107i to 107k of
Directive 2001/83/EC, under the second subparagraph of Article 31(1) thereof or
under Article 20(8) of Regulation (EC) No 726/2004.

2.           The amount of the fee is
laid down in Part III of the Annex.

3.           Where only one marketing
authorisation holder is involved in the procedure referred to in paragraph 1,
the Agency shall levy the total amount of the fee on that marketing
authorisation holder, as laid down in Part III of the Annex.

4.           Where two or more
marketing authorisation holders are involved in the procedure referred to in
paragraph 1, the Agency shall divide the total amount of the fee among those
marketing authorisation holders in accordance with Part III of the Annex.

5.           Where the marketing
authorisation holder referred to in paragraphs 2 or 3 is a small or medium-sized
enterprise, the amount payable by that marketing authorisation holder shall be
reduced as laid down in Part III of the Annex.

6.           The Agency shall levy the
fee under this Article by issuing a separate invoice to each marketing
authorisation holder involved in the procedure within thirty calendar days from
the public announcement of the procedure in accordance with Article 107j(1) of
Directive 2001/83/EC or from the date on which the matter was referred to the Agency
under the second subparagraph of Article 31(1) of Directive 2001/83/EC or under
Article 20(2) of Regulation (EC) No 726/2004. Fees due under this Article shall
be paid within thirty calendar days from the date on which the invoice is received
by the marketing authorisation holder.

Article 7

Annual
flat fee

1.           For its pharmacovigilance
activities relating to information technology systems under Article 24, Article
25a, Article 26, Article 57(1)(l) of Regulation (EC) No 726/2004, monitoring of
selected medical literature under Article 27 thereof and signal detection under
Article 28a thereof, the Agency shall levy once per year a flat fee as laid
down in Part IV of the Annex.

2.           The fee shall be levied on
holders of marketing authorisations for all medicinal products authorised in
the Union in accordance with Directive 2001/83/EC, on the basis of the
chargeable units corresponding to those products. Chargeable units
corresponding to products authorised in accordance with Regulation (EC)
No 726/2004 shall not be subject to the annual flat fee.
The total annual payable amount for each marketing authorisation holder shall
be calculated by the Agency on the basis of the chargeable units as defined in
Article 2(1) of this Regulation which correspond to the information recorded on
1 January of each year. This amount shall cover the period from 1 January to 31
December of that year.

3.           The amount of the annual
flat fee per chargeable unit is laid down in Part IV of the Annex.

4.           Where the marketing
authorisation holder is a small or medium-sized enterprise, the amount payable
by the marketing authorisation holder shall be reduced as laid down in Part IV of
the Annex.

5.           A reduced annual flat fee,
as laid down in Part IV of the Annex, shall apply in respect of medicinal
products referred to in Article 10(1) and Article 10a of Directive 2001/83/EC
and in respect of authorised homeopathic medicinal products and authorised
herbal medicinal products, as defined respectively in Article 1(5) and Article
1(30) of Directive 2001/83/EC.

6.           Where the marketing
authorisation holder of medicinal products referred to in paragraph 4 is a
small or medium-sized enterprise, only the reduction set out in paragraph 3
shall apply.

7.           The Agency shall levy the annual
flat fee by issuing invoices to marketing authorisation holders at the latest
on 31 January of every calendar year for that calendar year. Fees due under
this Article shall be paid within 30 calendar days from the date on which the
invoice is received by the marketing authorisation holder.

8.           The Agency shall retain
the fee revenue from the annual flat fee.

Article 8

Fee
reductions and exemptions

1.           Any marketing
authorisation holder claiming to be a small or medium-sized enterprise and,
therefore, to be entitled to a reduced fee under Articles 4 to 7, shall make a
declaration to that effect to the Agency within 30 calendar days from the
receipt of the invoice from the Agency. The Agency shall apply the
reduction on the basis of that declaration where the required conditions are
met.

2.           Any marketing
authorisation holder claiming to be a micro enterprise and to be entitled to
the exemption under Article 1 shall make a declaration to that effect to the
Agency within 30 calendar days from the receipt of the invoice from the Agency.
The Agency shall apply the exemption on the basis of that declaration.

3.           Any marketing authorisation
holder claiming to be entitled to a reduced annual flat fee under Article 7(5)
shall make a declaration to that effect to the Agency. The Agency shall apply
the reduction on the basis of that declaration where the required conditions
are met. Where the declaration is made by the marketing authorisation holder
after the receipt of the invoice from the Agency, the declaration shall be done
within 30 calendars days from the receipt of that invoice.

4.           The Agency may request, at
any time, evidence that the conditions for a reduction of fees or for an
exemption from fees are fulfilled. In that case, the marketing authorisation
holder claiming or having claimed to be entitled to a reduction or an exemption
under this Regulation, shall submit to the Agency the information necessary to
demonstrate compliance with the relevant conditions.

5.           Where a marketing
authorisation holder claiming or having claimed to be entitled to a reduction of
or an exemption from fees under this Regulation fails to demonstrate that it is
entitled to such a reduction or exemption, the amount of the fee laid down in
the Annex shall be increased by 10% and the Agency shall levy the resulting full
applicable amount or, as appropriate, the balance to the resulting full
applicable amount.

Article 9

Payment
of remuneration by the Agency to rapporteurs

1.           The Agency shall
remunerate rapporteurs in accordance with Article 3(2) in the following cases:

(c)
where the Member State has appointed a member of
the Pharmacovigilance Risk Assessment Committee who acts as rapporteur for the assessment
of periodic safety update reports referred to in Article 4;

(d)
where the Member State has appointed a representative
in the coordination group who acts as rapporteur in the context of the
assessment of periodic safety update reports referred to in Article 4;

(e)
where the Member State has appointed a member of
the Pharmacovigilance Risk Assessment Committee who acts as rapporteur for the assessment
of post-authorisation safety studies referred to in Article 5;

(f)
where the Member State has appointed a member of
the Pharmacovigilance Risk Assessment Committee who acts as rapporteur for the
referrals referred to in Article 6.

Where the Pharmacovigilance Risk Assessment
Committee or the coordination group decides to appoint a co-rapporteur, the remuneration
shall be divided between the rapporteur and the co-rapporteur.

2.           The corresponding amounts of
the remuneration for each of the activities listed in paragraph 1 are laid down
in Parts I, II and III of the Annex.

3.           The remuneration provided
for in paragraph 1 shall be paid only after the final assessment report for a
recommendation which is intended for adoption by the Pharmacovigilance Risk
Assessment Committee has been made available to the Agency.

4.           The remuneration provided
for in paragraph 1 for the work of the rapporteur and any related scientific
and technical support shall be without prejudice to the obligation of Member
States not to give committee members and experts instructions which are incompatible
with their own individual tasks as rapporteur or with the tasks and
responsibilities of the Agency.

5.           The remuneration shall be paid
in accordance with the written contract referred to in the first subparagraph of
Article 62(3) of Regulation (EC) No 726/2004. Any bank charges related to the
payment of that remuneration shall be borne by the Agency.

Article 10

Mode
of payment of the fee

1.           The fees shall be paid in Euro.

2.           Payments shall be made
only after the marketing authorisation holder has received an invoice issued by
the Agency.

3.           Payments shall be made by
means of a transfer to the bank account of the Agency. Any bank charges related
to the payment shall be borne by the marketing authorisation holder.

Article 11

Identification
of the payment of the fee

1.           In every payment the marketing
authorisation holder shall indicate the remittance reference. For payments made
by on-line payment system, the reference number generated is regarded as
remittance number.

2.           If the purpose of the
payment cannot be established, the Agency shall set a deadline by which the marketing
authorisation holder shall notify it in writing of the purpose of the payment.
If the Agency does not receive a notification of the purpose of the payment
before expiry of the deadline, the payment shall be considered invalid and the amount
concerned shall be refunded to the marketing authorisation holder.

Article 12

Date
of payment of the fee

The date on which the full amount of the
payment is received in the bank account held by the Agency shall be considered
to be the date on which the payment has been made. A deadline for payment shall
be considered to have been observed only if the full amount of the fee has been
paid in due time.

Article 13

Refund
of fee amounts paid in excess

1.           Excess amounts shall be
refunded by the Agency to the marketing authorisation holder. However, where an
amount paid in excess is under EUR 100 and the marketing authorisation holder concerned
has not expressly requested a refund, the amount paid in excess shall not be
refunded.

2.           It shall not be possible to
count any amounts paid in excess towards future payments to the Agency.

Article 14

Provisional
estimate of Agency budget

The Agency shall, when producing an
estimate of the overall expenditure and income for the following financial year
in accordance with Article 67(6) of Regulation (EC) No 726/2004, include
detailed information on income from fees relating to pharmacovigilance
activities. This information shall distinguish between the annual flat fee and
the fees for each procedure referred to in Article 3(a). The Agency shall also
provide specific analytical information on its revenue and expenditure related
to pharmacovigilance activities, allowing to distinguish between the annual
flat fee and each of the fees for procedures referred to in Article 3(a).

Article 15

Transparency
and monitoring

1.           The amounts and rates laid
down in Parts I to IV of the Annex shall be published on the website of the
Agency.

2.           The Executive Director of
the Agency shall provide the Commission and the Management Board annually with
information on the components that may have a bearing on the costs to be
covered by the fees provided for in this Regulation. This information shall include
a cost breakdown related to the previous year and a forecast for the following
year. The Executive Director of the Agency shall also provide the Commission
and the Management Board once per year with the performance information set out
in Part V of the Annex based on the performance indicators referred to in
paragraph 3.

3.           Within one year from the
entry into force of this Regulation, the Agency shall adopt a set of performance
indicators taking into account the information listed in Part V of the Annex.

4.           The inflation rate as
measured by means of the European Index of Consumer prices as published by
Eurostat pursuant to Regulation (EC) No 2494/95 shall be monitored in relation to
the amounts set out in the Annex. The monitoring shall take place for the first
time after this Regulation has been applied during a full calendar year and,
thereafter, annually.

5.           In view of the monitoring
referred to in paragraph 4, the Commission may, where necessary, adjust the
amounts of the fees and the amounts of the remuneration of rapporteurs laid
down in the Annex, in accordance with Article 16. Those adjustments shall take
effect on 1 April following the entry into force of the corresponding amending
act.

Article 16

Amendment

1.           The Commission shall be
empowered to adopt delegated acts to amend Parts I to V of the Annex.

2.           Any amendments to the
amounts shall be based on an evaluation of the costs of the Agency and the
costs of the assessments provided by the rapporteurs as laid down in Article 9
or on the monitoring of the inflation rate referred to in Article 15(4).

Article 17

Exercise
of the delegation

1.           The power to adopt
delegated acts is conferred on the Commission subject to the conditions laid down
in this Article.

2.           The power to adopt
delegated acts referred to in Article 16 shall be conferred on the Commission
for an indeterminate period of time from [*].

3.           The delegation of powers
referred to in Article 16 may be revoked at any time by the European Parliament
and by the Council. A decision to revoke shall put an end to the delegation of
the power specified in that decision. It shall take effect the day following
the publication of the decision in the Official Journal of the European Union
or at the later date specified therein. It shall not affect the validity of any
delegated acts already in force.

4.           As soon as it adopts a
delegated act, the Commission shall notify it simultaneously to the European
Parliament and to the Council.

5.           A delegated act adopted pursuant
to Article 16 shall enter into force only if no objection has been expressed
either by the European Parliament or the Council within a period of two months
of notification of that act to the European Parliament and the Council or if,
before the expiry of that period, the European Parliament and the Council have
both informed the Commission that they will not object. That period shall be
extended by two months at the initiative of the European Parliament and the
Council.

Article 18

Transitional
provisions

The fees referred to in Articles 4, 5 and 6 and
Parts I, II and III of the Annex shall not apply to those procedures at Union level
which are initiated before the fortieth day following the entry into force of
this Regulation.

Article 19

Entry
into force and application

1.           This Regulation shall
enter into force on the twentieth day following that of its publication in the
Official Journal of the European Union.

2.           The annual flat fee
referred to in Article 7 and specified in Part IV of the Annex shall be levied for
the first time by [31 January or by 1 July following the entry into force of
this Regulation whichever date is the earliest], and by 31 January every year
thereafter. [In case the annual flat fee is levied for the first time on 1
July, 50 % of the full flat fee shall be levied.][To be adapted by the
legislator]

This Regulation shall be binding
in its entirety and directly applicable in all Member States.

Done at Brussels,

For the European Parliament                       For
the Council

The President                                                 The
President

ANNEX

PART
I

Fee
for assessment of periodic safety update reports referred to in Article 4: amounts
levied by the Agency and level of remuneration of rapporteurs

1.           The
fee for the assessment of
periodic safety update reports is EUR 19 500 per procedure. The corresponding
remuneration of the rapporteur is EUR 13 100.

2.           In
application of Article 4(5), small and medium-sized enterprises shall pay 60 %
of the applicable amount.

3.           For
the purpose of calculating the amount to be levied on each marketing
authorisation holder in application of Article 4(4), the Agency shall calculate
the proportion of chargeable units held by each marketing authorisation holder
concerned of the total number of chargeable units held by all marketing
authorisation holders involved in the procedure.

The share payable by each marketing
authorisation holder shall be calculated by:

(i) dividing the total amount of the fee among
the marketing authorisation holders concerned proportionately to the number of
chargeable units,

(ii) subsequently applying the reduction as per
paragraph 2 of Part I of this Annex and the exemption referred to in Article
1(3), where relevant.

4.           Where
reductions and exemptions apply, the remuneration of the rapporteur shall be
adapted proportionally. Where the Agency subsequently collects the full
applicable amount including the 10 % increase as provided for in Article
8(5), the remuneration of the rapporteur shall be adapted proportionally.

PART II

Fee
for assessment of a post-authorisation safety study referred to in Article 5: amounts
levied by the Agency and level of remuneration rapporteurs

1.           The
fee for the assessment of a post authorisation safety study is EUR 43 000.
The corresponding remuneration of the rapporteur is EUR 18 200.

2.           In
application of Article 5(4), small and medium-sized enterprises shall pay 60 %
of the applicable amount.

3.           Where
marketing authorisation holders concerned conduct a joint post-authorisation
safety study referred to in Article 5(3), the amount payable by each marketing
authorisation holder shall be levied by the Agency by evenly dividing the total
amount of the fee among those marketing authorisation holders. Where relevant, the
reduction laid down in paragraph 2 of Part II of this Annex or, where
appropriate, the exemption referred to in Article 1(3), shall be applied to the
share payable by the marketing authorisation holder.

4.           Where
reductions and exemptions apply, the remuneration of the rapporteur shall be
adapted proportionally. Where the Agency subsequently collects the full
applicable amount including the 10 % increase as provided for in Article
8(5), the remuneration of the rapporteur shall be adapted proportionally.

PART III

Fee
for assessment in the context of referrals initiated as a result of the
evaluation of pharmacovigilance data referred to in Article 6: amounts levied
by the Agency and level of remuneration of rapporteurs

1.           The
fee for the assessment of the procedure referred to in Article 6(1) is EUR 168 600.
The corresponding remuneration of the rapporteur is EUR 45 100.

2.           In
application of Article 6(5), small and medium-sized enterprises shall pay 60 %
of the applicable amount.

3.           For
the purpose of calculating the amount to be levied on each marketing
authorisation holder in application of Article 6(4), the Agency shall calculate
the proportion of chargeable units held by each marketing authorisation holder
concerned of the total number of chargeable units held by all marketing
authorisation holders involved in the procedure.

The amount payable by each marketing
authorisation holder shall be calculated by:

(i) dividing the total amount of the fee among
the marketing authorisation holders concerned proportionately to the number of
chargeable units,

(ii) subsequently applying the reduction laid
down in paragraph 2 of Part II of this Annex and the exemption referred to in
Article 1(3), where relevant.

Where reductions and exemptions apply, the
remuneration of the rapporteur shall be adapted proportionally. Where the
Agency subsequently collects the full applicable amount including the 10 %
increase as provided for in Article 8(5), the remuneration of the rapporteur
shall be adapted proportionally.

PART IV

Annual
flat fee referred to in Article 7

1.           The
annual flat fee is EUR 60 per chargeable unit.

2.           In
application of Article 7(4), small and medium-sized enterprises shall pay 60 %
of the applicable amount.

3.           Holders
of marketing authorisations for medicinal products referred to in Article 7(5) shall
pay 80 % of the amount applicable to the chargeable units corresponding to
those products.

PART V

Performance
information

The following information shall relate to each
calendar year:

Number of Agency staff involved in pharmacovigilance activities as per the legislation applicable during the reference period, specifying staff allocated to activities corresponding to each of the fees referred to in Articles 4 to 7.

Number of hours outsourced to third parties with specification of the activities concerned and cost incurred.

Overall pharmacovigilance costs and a breakdown of staff and non-staff costs relating to activities corresponding to each of the fees referred to in Articles 4 to 7.

Number of procedures relating to the assessment of periodic safety update reports, as well as number of marketing authorisation holders and number of chargeable units per procedure; number of reports submitted per procedure and number of marketing authorisation holders that have submitted a joint periodic safety update report.

Number of procedures relating to the assessment of post-authorisation safety studies; number of marketing authorisation holders having carried out such studies and number of marketing authorisation holders that have submitted a joint study.

Number of procedures relating to the referrals initiated on the basis of pharmacovigilance data as well as number of marketing authorisation holders and number of chargeable units involved per marketing authorisation holder and per procedure.

Number of marketing authorisation holders that have claimed a small and medium-sized enterprise status involved in each procedure; number of marketing authorisation holders whose claim has been denied. Number of marketing authorisation holders that have claimed a micro enterprise status; number of marketing authorisation holders whose claim for fee exemption has been denied.

Number of marketing authorisation holders of medicinal products referred to in Article 7(5) that have benefitted from reduced annual flat fees; number of chargeable units per marketing authorisation holders concerned.

Number of invoices sent out/ annual fees charged in respect of the annual flat fee and average and overall amount invoiced to marketing authorisation holders. Number of marketing authorisation holders that have claimed a small and medium-sized enterprise or a micro enterprise status for each annual application of the annual flat fee; number of marketing authorisation holders whose claim has been denied.

Attribution of rapporteurships and co-rapporteurships per Member State per type of procedure

LEGISLATIVE
FINANCIAL STATEMENT

1.           FRAMEWORK OF THE PROPOSAL/INITIATIVE

1.1.        Title of the
proposal/initiative

REGULATION
OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL

on fees
payable to the European Medicines Agency (EMA) for the conduct of
pharmacovigilance activities in respect of medicinal products for human use

1.2.        Policy area(s) concerned
in the ABM/ABB structure[21]

Public
Health (Heading 3B of MFF)

1.3.        Nature of the
proposal/initiative

 ̈ The proposal/initiative relates to a new action

 ̈ The
proposal/initiative relates to a new action following a pilot
project/preparatory action[22]

þ The
proposal/initiative relates to the extension of an existing action

 ̈ The
proposal/initiative relates to an action redirected towards a new action

1.4.        Objectives

1.4.1.     The Commission's
multiannual strategic objective(s) targeted by the proposal/initiative

Resource-efficient,
smart and inclusive growth.

1.4.2.     Specific objective(s) and
ABM/ABB activity(ies) concerned

Specific
objective No

Ensure
proper implementation of measures to monitor safety of medicines through
implementation at the level of the Union of the pharmacovigilance legislation
of the Union

ABM/ABB
activity(ies) concerned

Public
Health (Heading 3B of MFF)

1.4.3.     Expected result(s) and
impact

Specify the effects which the proposal/initiative
should have on the beneficiaries/groups targeted.

The main
effect is the introduction of fees to be paid by marketing authorisation
holders of medicinal products for human use for the conduct of
pharmacovigilance activities by the European Medicines Agency as per the
applicable legislation, including scientific assessment performed by rapporteurs
in the framework of Union-wide pharmacovigilance procedures.

The
expected impact on the EMA is to be able to collect fees to ensure adequate
financing in order to cover the estimated cost for the conduct of
pharmacovigilance activities as assigned to it by the 2010 legislation on
pharmacovigilance that became applicable in July 2012.

Marketing
authorisation holders (MAH) are proposed to be charged a fee per procedure when
involved in one of the Union-wide pharmacovigilance procedures. It is also
proposed that all MAH of medicinal products for human use with a valid
authorisation be charged a flat-rate fee for general pharmacovigilance
activities of the EMA, as assigned to the Agency by the applicable legislation
on pharmacovigilance.

It is
proposed that rapporteurs from the national competent authorities be
remunerated for the assessment services that that provide in the framework of
the Union-wide pharmacovigilance procedures. This remuneration, based on
average cost estimations, is included in the proposed fees.

1.4.4.     Indicators of results and
impact

Specify the indicators for monitoring implementation
of the proposal/initiative.

The
monitoring will be related to the implementation of the annual budget of the
EMA. The annual activity report on the performance of the EMA will provide
reliable performance information as provided for in the proposed Regulation and
key indicators such as:

–
the actual number of Union-wide
pharmacovigilance procedures and their qualitative content,

–
the amount of actual cost for each type of
procedure and for general pharmacovigilance activities,

–
the minimum, maximum and average number of
marketing authorisations and marketing authorisation holders (MAH) per
procedure, as well as other indicators such as ranges representing a high
percentage of the cases,

–
the annual fee revenue per procedure and the
annual fee revenue from the flat fee.

Based on
data on actual cost and fee revenue, the Commission may consider whether there
is a need to revise the fees, after experience has been gained.

1.5.        Grounds for the
proposal/initiative

1.5.1.     Requirement(s) to be met in
the short or long term

The new
pharmacovigilance legislation is already applicable and it foresees that
pharmacovigilance activities be financed through new fees. The proposed
legislation will only deal with fees for EMA (and not fees charged by national
competent authorities for which the Union is not competent).

1.5.2.     Added value of involvement
of the Union

The
European Medicines Agency is a European decentralised Agency set up by
Regulation (EC) No 726/2004. Hence, decisions on its funding are to be taken at
the level of the Union. Only the Union can act to introduce these fees for
pharmacovigilance.

1.5.3.     Lessons learned from
similar experiences in the past

Feedback
from public consultation that took place from 18 June 2012 to 15 September 2012
indicated that fees for pharmacovigilance should be cost-based and as much as
possible follow the principle of payment for service.

1.5.4.     Compatibility and possible
synergy with other appropriate instruments

The
proposed Regulation will apply in parallel to the existing Council Regulation
(EC) No 297/95 on fees payable to the EMA for the Evaluation of Medicinal
Products.

1.6.        Duration and financial
impact

 ̈ Proposal/initiative of limited duration

(1)
 ̈ Proposal/initiative in effect from [DD/MM]YYYY to [DD/MM]YYYY

(2)
 ̈ Financial impact from YYYY to YYYY

þ Proposal/initiative of unlimited duration

–
Implementation with a start-up period from YYYY
to YYYY,

–
followed by full-scale operation.

1.7.        Management mode(s)
envisaged[23]

 ̈ Centralised direct management by the
Commission

þ Centralised indirect management with the
delegation of implementation tasks to:

–
 ̈ executive agencies

–
þ bodies set up by
the Communities[24]

–
 ̈ national public-sector bodies/bodies with public-service mission

(3)
 ̈ persons entrusted with the implementation of specific actions
pursuant to Title V of the Treaty on European Union and identified in the
relevant basic act within the meaning of Article 49 of the Financial Regulation

 ̈ Shared management with the Member States

 ̈ Decentralised management with third
countries

 ̈ Joint management with international
organisations (to be specified)

If more than one management mode is indicated, please
provide details in the "Comments" section.

2.           MANAGEMENT MEASURES

2.1.        Monitoring and reporting
rules

Specify frequency and conditions.

The Agency will provide the Commission and the Management Board twice per year with detailed and aggregated performance information and indicators relating to pharmacovigilance activities and fees.

2.2.        Management and control
system

2.2.1.     Risk(s) identified

Insufficient fee income, given the difficulty to predict the exact actual frequency, scope and cost of all the Union-wide pharmacovigilance procedures and activities occurring in a given year.

Incomplete collection of invoiced fees.

2.2.2.     Control method(s) envisaged

Regular monitoring and reporting from the Agency to the Commission on the level of performance, the level of collection of fees and unitary and aggregated cost-related components relevant to the estimation of fee levels.

2.2.3.     Costs and benefits of
controls and probable non-compliance rate

Administrative procedures of the Agency will be set up so that existing monitoring tables, cost-account tables and activity-based system provide information on cost breakdown of procedures and activities that will be funded by the fees set up by this Regulation.

2.3.        Measures to prevent fraud
and irregularities

Specify existing or envisaged prevention and
protection measures.

In addition
to the application of all regulatory control mechanisms, the responsible
Commission's services will devise an anti-fraud strategy in line with the
Commission's anti-fraud strategy (CAFS) adopted on 24 June 2011 in order to
ensure inter alia that its internal anti-fraud related controls are fully
aligned with the CAFS and that its fraud risk management approach is geared to
identify fraud risk areas and adequate responses. Where necessary, networking
groups and adequate IT tools dedicated to analysing fraud cases related to the
financing implementing activities of this Regulation will be set up. In
particular a series of measures will be put in place such as:

–
decisions, agreements and contracts resulting
from the financing implementing activities of this Regulations will expressly
entitle EMA, the Commission, including OLAF, and the Court of Auditors to
conduct audits, on-the-spot checks and inspections;

–
regular training on issues related to fraud and
irregularities is given to all staff involved in fee and contract management as
well as to auditors and controllers.

3.           ESTIMATED FINANCIAL IMPACT OF THE
PROPOSAL/INITIATIVE

3.1.        Heading(s) of the
multiannual financial framework and expenditure budget line(s) affected

–
Existing budget lines

In order of multiannual financial framework headings and budget lines.

Heading of multiannual financial framework 3 || Budget line || Type of expenditure || Contribution

Number 17.0310* Subsidy to the European Medicines Agency || Diff./non-diff.[25] || from EFTA countries[26] || from candidate countries[27] || from third countries || within the meaning of Article 18(1)(aa) of the Financial Regulation

|| [XX.YY.YY.YY] || non-diff. || YES || NO || NO || NO

*17.0312
as from 01/01/2014

–
New budget lines requested N/A

In order of multiannual financial framework headings and
budget lines.

Heading of multiannual financial framework || Budget line || Type of expenditure || Contribution

Number [Heading.........................................] || Diff./non-diff. || from EFTA countries || from candidate countries || from third countries || within the meaning of Article 18(1)(aa) of the Financial Regulation

|| [XX.YY.YY.YY] || || YES/NO || YES/NO || YES/NO || YES/NO

- The
annual subsidy to the EMA is paid under this budget line. However, all
pharmacovigilance activities under this proposal are considered to be
fee-financed. Consequently, no impact is foreseen on the budget of the Union.

3.2.        Estimated impact on
expenditure

This part must be
completed on the spreadsheet on budget data of an administrative nature (second
document in the annex to this financial statement) to be uploaded to CISNET for
interdepartmental consultation purposes.

3.2.1.     Summary of estimated impact
on expenditure : N/A

EUR million (to three decimal places)

Heading of multiannual financial framework: || Number || [Heading ...........................................................................................]

DG: <.......> || || || Year N[28] || Year N+1 || Year N+2 || Year N+3 || Enter as many years as necessary to show the duration of the impact (see point 1.6) || TOTAL

 Operational appropriations || || || || || || || ||

Number of budget line || Commitments || (1) || || || || || || || ||

Payments || (2) || || || || || || || ||

Number of budget line || Commitments || (1a) || || || || || || || ||

Payments || (2a) || || || || || || || ||

Appropriations of an administrative nature financed from the envelope of specific programmes[29] || || || || || || || ||

Number of budget line || || (3) || || || || || || || ||

TOTAL appropriations for DG <.......> || Commitments || =1+1a +3 || || || || || || || ||

Payments || =2+2a +3 || || || || || || || ||

 TOTAL operational appropriations || Commitments || (4) || || || || || || || ||

Payments || (5) || || || || || || || ||

 TOTAL appropriations of an administrative nature financed from the envelope for specific programmes || (6) || || || || || || || ||

TOTAL appropriations under HEADING <....> of the multiannual financial framework || Commitments || =4+ 6 || || || || || || || ||

Payments || =5+ 6 || || || || || || || ||

If more than one heading is affected by the proposal /
initiative:

 TOTAL operational appropriations || Commitments || (4) || || || || || || || ||

Payments || (5) || || || || || || || ||

 TOTAL appropriations of an administrative nature financed from the envelope for specific programmes || (6) || || || || || || || ||

TOTAL appropriations under HEADINGS 1 to 4 of the multiannual financial framework (Reference amount) || Commitments || =4+ 6 || || || || || || || ||

Payments || =5+ 6 || || || || || || || ||

Heading of multiannual financial framework || 5 || ‘Administrative expenditure’

EUR million (to three decimal places)

|| || || Year N || Year N+1 || Year N+2 || Year N+3 || Enter as many years as necessary to show the duration of the impact (see point 1.6) || TOTAL

DG: <.......> ||

 Human resources || || || || || || || ||

 Other administrative expenditure || || || || || || || ||

TOTAL DG <.......> || Appropriations || || || || || || || ||

TOTAL appropriations for HEADING 5 of the multiannual financial framework || (Total commitments = Total payments) || || || || || || || ||

EUR million (to three decimal places)

|| || || Year N[30] || Year N+1 || Year N+2 || Year N+3 || Enter as many years as necessary to show the duration of the impact (see point 1.6) || TOTAL

TOTAL appropriations under HEADINGS 1 to 5 of the multiannual financial framework || Commitments || || || || || || || ||

Payments || || || || || || || ||

3.2.2.     Estimated impact on
operational appropriations

–
þ The proposal/initiative does not require the use of
operational appropriations

–
 ̈ The proposal/initiative requires the use of operational
appropriations, as explained below:

Commitment appropriations in EUR million (to three
decimal places)

Indicate objectives and outputs ò || || || Year N || Year N+1 || Year N+2 || Year N+3 || Enter as many years as necessary to show the duration of the impact (see point 1.6)) || TOTAL

OUTPUTS

Type[31] || Average cost || Number || Cost || Number || Cost || Number || Cost || Number || Cost || Number || Cost || Number || Cost || Number || Cost || Total Number || Total Cost

SPECIFIC OBJECTIVE No 1[32]... || || || || || || || || || || || || || || || ||

- Output || || || || || || || || || || || || || || || || || ||

- Output || || || || || || || || || || || || || || || || || ||

- Output || || || || || || || || || || || || || || || || || ||

Subtotal for specific objective n° 1 || || || || || || || || || || || || || || || ||

SPECIFIC OBJECTIVE n° 2... || || || || || || || || || || || || || || || ||

- Output || || || || || || || || || || || || || || || || || ||

Subtotal for specific objective n° 2 || || || || || || || || || || || || || || || ||

TOTAL COST || || || || || || || || || || || || || || || ||

3.2.3.     Estimated impact on
appropriations of an administrative nature

3.2.3.1.  Summary

–
þ The proposal/initiative does not require the use of
appropriations of an administrative nature

–
 ̈ The proposal/initiative requires the use of appropriations of
an administrative nature, as explained below:

EUR million (to
three decimal places)

|| Year N[33] || Year N+1 || Year N+2 || Year N+3 || Enter as many years as necessary to show the duration of the impact (see point 1.6) || TOTAL

HEADING 5 of the multiannual financial framework || || || || || || || ||

Human resources || || || || || || || ||

Other administrative expenditure || || || || || || || ||

Subtotal HEADING 5 of the multiannual financial framework || || || || || || || ||

Outside HEADING 5[34] of the multiannual financial framework || || || || || || || ||

Human resources || || || || || || || ||

Other expenditure of an administrative nature || || || || || || || ||

Subtotal outside HEADING 5 of the multiannual financial framework || || || || || || || ||

TOTAL || || || || || || || ||

The administrative
appropriations required will be met by the appropriations of the DG which are
already assigned to management of the action and/or which have been redeployed
within the DG, together if necessary with any additional allocation which may
be granted to the managing DG under the annual allocation procedure and in the
light of budgetary constraints.

3.2.3.2.  Estimated requirements of
human resources N/A

–
 ̈ The proposal/initiative does not require the use of human
resources.

–
 ̈ The proposal/initiative requires the use of human resources,
as explained below:

Estimate to be expressed in full time
equivalent units

|| Year N || Year N+1 || Year N+2 || Year N+3 || Enter as many years as necessary to show the duration of the impact (see point 1.6)

 Establishment plan posts (officials and temporary agents) ||

XX 01 01 01 (Headquarters and Commission’s Representation Offices) || || || || || || ||

XX 01 01 02 (Delegations) || || || || || || ||

XX 01 05 01 (Indirect research) || || || || || || ||

10 01 05 01 (Direct research) || || || || || || ||

 External personnel (in Full Time Equivalent unit: FTE)[35] ||

XX 01 02 01 (CA, INT, SNE from the "global envelope") || || || || || || ||

XX 01 02 02 (CA, INT, JED, LA and SNE in the delegations) || || || || || || ||

XX 01 04 yy[36] || - at headquarters || || || || || || ||

- in delegations || || || || || || ||

XX 01 05 02 (CA, SNE, INT - Indirect research) || || || || || || ||

10 01 05 02 (CA, SNE, INT - Direct research) || || || || || || ||

Other budget lines (specify) || || || || || || ||

TOTAL || || || || || || ||

XX is the policy area or budget title
concerned.

The human resources required will be met by staff from
the DG who are already assigned to management of the action and/or have been
redeployed within the DG, together if necessary with any additional allocation
which may be granted to the managing DG under the annual allocation procedure
and in the light of budgetary constraints.

Description of
tasks to be carried out:

Officials and temporary staff ||

External staff ||

3.2.4.     Compatibility with the current
multiannual financial framework

–
þ Proposal/initiative is compatible the current multiannual
financial framework.

–
 ̈ Proposal/initiative will entail reprogramming of the relevant
heading in the multiannual financial framework.

Explain what reprogramming is required, specifying the
budget lines concerned and the corresponding amounts.

[...]

–
 ̈ Proposal/initiative requires application of the flexibility
instrument or revision of the multiannual financial framework.[37]

Explain what is required, specifying the headings and
budget lines concerned and the corresponding amounts.

[...]

3.2.5.     Third-party contributions

–
þ The proposal/initiative does not provide for co-financing by third
parties.

–
 ̈ The proposal/initiative provides for the co-financing estimated
below:

Appropriations in EUR million (to three decimal
places)

|| Year N || Year N+1 || Year N+2 || Year N+3 || Enter as many years as necessary to show the duration of the impact (see point 1.6) || Total

Specify the co-financing body || || || || || || || ||

TOTAL appropriations cofinanced || || || || || || || ||

3.3.        Estimated impact on
revenue

–
þ Proposal/initiative has no financial impact on revenue.

–
 ̈ Proposal/initiative has the following financial impact:

–
 ̈ on own resources

–
 ̈ on miscellaneous revenue

EUR million (to three decimal places)

Budget revenue line: || Appropriations available for the current financial year || Impact of the proposal/initiative[38]

Year N || Year N+1 || Year N+2 || Year N+3 || Enter as many years as necessary to show the duration of the impact (see point 1.6)

Article ............. || || || || || || || ||

For miscellaneous ‘assigned’ revenue, specify the
budget expenditure line(s) affected.

[...]

Specify the method for calculating the impact on
revenue.

[...]

ANNEX: DETAILS OF CALCULATIONS

General remarks

It is proposed that the entire cost
relating to pharmacovigilance activities at the level of the Union as per the
applicable legislation is recouped through fees. Cost estimations and
calculations in this Annex are based on this principle and,
therefore, the proposed measures are not expected to have any financial impact
on the budget of the Union.

The cost estimations comprise cost of the Agency
activities and cost of rapporteurs' assessment activities. The amounts to be
respectively retained by the Agency and paid to rapporteurs where assessment
has taken place are estimated accordingly.

Amounts that are proposed for remuneration
of rapporteurs are based on the estimated average cost of assessment work in
the context of the pharmacovigilance procedures of the Union.

The costing table provides four general
headings of cost:

(1)          Periodic Safety Update
Reports assessment (procedural cost, both for the Agency and rapporteurs of
Member States)

(2)          Post Authorisation Safety
Study assessment (procedural cost, both for the Agency and rapporteurs of
Member States)

(3)          Pharmacovigilance (Safety)
Referral (procedural cost, both for the Agency and rapporteurs of Member States)

(4)          Other cost: non-procedural
cost, only incurred by the Agency. This heading includes ICT systems (e.g.
EudraVigilance database, repository of periodic safety update reports),
literature monitoring, ADR ('adverse drug reaction': reports on adverse effects
of medicines) management and signal detection and risk management, within the scope
of the Agency's responsibilities.

Remuneration of rapporteurs of Member
States is foreseen for work provided with respect to headings (1), (2) and (3),
i.e. for the three Union-wide pharmacovigilance procedures. These three
procedures will entail procedure-based fees, calculated based on cost
estimation of the Agency's and rapporteurs' activities.

As regards the EMA's cost in heading
'Other', it is proposed to recoup this cost through an annual flat fee to be
charged to marketing authorisation holders for authorised products registered by
the Agency based on the list referred to in Article 57(2) of Regulation EC No
726/2004, using chargeable units as defined in the proposed Regulation. Cost
estimations under this heading (4) include only costs of the Agency, whereas
Member States may continue charging national fees to cover costs at national
level.

Periodic Safety Update Reports
assessment

The estimated number of periodic safety
update reports assessment procedures expected by the Agency is 600 per year.
The total estimated cost related to these assessments is € 11,3 m per year
(€ 3,4 m Agency cost and € 7,9 m rapporteur remuneration). The
average cost for the proposed procedure-related fee is € 19 500 per
procedure[39].
The average part of the cost on which the proposed rapporteur remuneration is
based is € 13 100 per procedure.

Post-Authorisation Safety Study
assessment

The estimated number of post-authorisation
safety study assessments expected by the Agency is 35 per year. The total
estimated cost related to these assessments is € 1,5 m per year
(€ 0,9 m Agency cost and € 0,6 m rapporteur remuneration).
The average cost on which the proposed procedure-related fee is based is
€ 43 000 per procedure. The average part of the cost on which the proposed
rapporteur remuneration is based is € 18 200 per procedure.

Pharmacovigilance Referral assessment

The estimated number of Pharmacovigilance
Referral assessments expected by the Agency is 40 per year. The total estimated
cost related to these assessments is € 6,7 m per year (€ 4,9 m
Agency cost and € 1,8 m rapporteur remuneration). The average cost on
which the proposed procedure-related fee is based is € 168 600 per procedure.
The average part of the cost on which the proposed rapporteur remuneration is
based is € 45 100 per procedure.

Mechanism of charging the fee for procedures
for periodic safety update reports, post-authorisation safety studies and pharmacovigilance
referrals

For periodic
safety update reports and pharmacovigilance referral procedures, the fee will
be divided among marketing authorisation holders involved in the procedure by
charging them proportionately to the respective number of marketing
authorisations (chargeable units) held by each marketing authorisation holder.
For post-authorisation safety study procedures, the fee is proposed to be
divided among all marketing authorisation holders having the obligation to
produce the study by charging equal parts to each marketing authorisation
holder. Further division of the cost may take place between marketing authorisation
holders which have taken part in the study.

Furthermore, the
amount charged to marketing authorisation holders that are small and
medium-sized enterprises will be reduced to 60% and marketing authorisation
holders that are micro-enterprises will not be charged any fee.

Mechanism of
remunerating rapporteurs

Rapporteurs'
remuneration is included in the calculation of the fee for each Union-wide
pharmacovigilance procedure. Full rapporteur remuneration is based on estimated
average cost per procedure. The applicable rapporteur remuneration follows the
same pattern as the actual fee revenue per procedure, i.e. a reduced fee revenue
entails a proportionately reduced rapporteur remuneration.

Other pharmacovigilance activities of
the Agency

This heading of estimated cost of the
Agency is taken into account in the calculations of the annual flat fee charged
to all marketing authorisation holders with respect to their marketing
authorisations (chargeable units, as recorded by the Agency based on the list
laid down in Article 57(2) of Regulation (EC) No 726/2004). Marketing
authorisations of centrally authorised products are not subject to this fee, as
they are already charged an annual fee, in accordance with Council Regulation
(EC) No 297/95, which is assumed to cover non-procedure related
pharmacovigilance activities for those products.

The total estimated cost for the Agency under
this heading is € 19,1 m. Calculations in the impact assessment based
on this figure led to a proposed amount for the full flat fee of € 60 per
marketing authorisation, that should be counted in a consistent way for all marketing
authorisation holders based on chargeable units. It is proposed that marketing
authorisation holders that are small and medium-sized enterprises pay 60% of
the full fee and that micro-enterprises be exempted from the payment of the annual
flat fee. Furthermore, a fee reduction of 20% is proposed for marketing
authorisation holders for medicinal products referred to in Article 10(1) and
Article 10a of Directive 2001/83/EC, as well as for authorised herbal medicinal
products and authorised homeopathic medicinal products.

Workload and cost estimation tables

Summary table of overall cost estimations

Activities || EMA || Rapporteurs / NCA || Total

Union-wide pharmacovigilance procedures

PSUR assessment || €3 435 671 || €7 857 374 || €11 293 045

PASS assessment || €866 456 || €636 778 || €1 503 234

Pharmacovigilance referrals assessment || €4 887 616 || €1 803 405 || €6 691 021

Subtotal procedures || €9 189 743 || €10 297 557 || €19 487 300

Other pharmacovigilance activities of the EMA

Other || €18 825 914 || €232 606 || €19 058 520

Grand total || €28 015 657 || €10 530 163 || €38 545 820

1. Periodic safety update reports assessment

Activities || EMA || Rapporteurs / NCA || Total cost

|| || || || || Nr of hours required || Hourly rate / wage || Frequency per year || EMA total || No. of hours required || Hourly rate / wage || Frequency per year || Rapporteur total

PSUR assessment || 1 || || || Preparation of list of harmonised submission dates for selected active substances || 53,75 || 124,1 || 2 || €13 341 || || || || ||

2 || || || Preparation of PRAC advice and updated EURD list following request for changes from MAH || 21,5 || 124,1 || 10 || €26 682 || || || || ||

3 || || || Validation of PSUR, preparation of data for Rapporteur from Eudravigilance database and other sources || 11,9 || 124,1 || 600 || €886 074 || || || || ||

5,1 || 79,5 || 600 || €243 270 || || || || ||

4 || || || Preparation of PRAC, CHMP/CMDh outcome || 21,2 || 124,1 || 600 || €1 578 552 || || || || ||

9,1 || 79,5 || 600 || €434 070 || || || || ||

5 || || || PRAC Staff time related to PSUR || 81 || 124,1 || 11 || €110 573 || 194 || 109 || 11 || €232 606 ||

81 || 79,5 || 11 || €70 835 || || || || ||

6 || || || CHMP/CMDh Staff time related to PSUR || 27 || 124,1 || 11 || €36 858 || 32 || 109 || 11 || €38 368 ||

40,5 || 79,5 || 11 || €35 417 || || || || ||

|| 6a || || || Evaluation/assessment of PSUR applications || || || || || 116 || 109 || 600 || €7 586 400 ||

|| || || ||  Subtotal PSUR || || || || €3 435 671 || || || || €7 857 374 || €11 293 045

|| || || || Average per procedure || || || || €5 726 || || || || €13 096 || €18 822

2. Post-authorisation safety study assessment

Activities || EMA || Rapporteurs / NCA || Total cost

|| || || || || Nr of hours required || Hourly rate / wage || Frequency per year || EMA total || No. of hours required || Hourly rate / wage || Frequency per year || Rapporteur total

PASS assessment || 7 || || PASS Protocol || Preparation of request including scientific questions and pre-submission meeting || 25 || 124,1 || 35 || €108 588 || || || || ||

8 || || Summary outcome of protocol and outcome documents for PRAC || 42,5 || 124,1 || 35 || €184 599 || || || || ||

9 || || Summary outcome of protocol amendments and outcome documents for PRAC || 27,5 || 124,1 || 35 || €119 446 || || || || ||

10 || || || Summary of study report and outcome of report documents for PRAC and CHMP/CMDh || 60 || 124,1 || 35 || €260 610 || || || || ||

11 || || || PRAC Staff time related to PASS || 54 || 124,1 || 11 || €73 715 || 130 || 109 || 11 || €155 870 ||

54 || 79,5 || 11 || €47 223 || || || || ||

12 || || || CHMP/CMDh Staff time related to PASS || 27 || 124,1 || 11 || €36 858 || 32 || 109 || 11 || €38 368 ||

40,5 || 79,5 || 11 || €35 417 || || || || ||

|| 12a || || || Evaluation/assessment of PASS applications || || || || || 116 || 109 || 35 || €442 540 ||

|| || || || Sub-total PASS || || || || €866 456 || || || || €636 778 || €1 503 234

|| || || || Average per procedure || || || || €24 756 || || || || €18 194 || €42 950

3. Pharmacovigilance referral assessment

Activities || EMA || Rapporteurs / NCA || Total cost

|| || || || || Nr of hours required || Hourly rate / wage || Frequency per year || EMA total || No. of hours required || Hourly rate / wage || Frequency per year || Rapporteur total

Pharmacovigilance Refferal || 13 || || Initiation ||  Preparation of procedure including scope of procedure, identification of products involved, List of Questions, analyses of in-house data || 73,8 || 124,1 || 40 || €366 343 || || || || ||

73,8 || 79,5 || 40 || €234 684 || || || || ||

14 || || Assessment || Preparation of outcome documents for PRAC and CHMP/CMDh (temporary measures, list of outstanding issues, recommendations, opinions), analyses of in-house data, organisation of oral explanations, scientific advisory groups/expert meetings and public hearings || 300 || 124,1 || 40 || €1 489 200 || || || || ||

300 || 79,5 || 40 || €954 000 || || || || ||

15 || || post - assessment || Preparation and publication of information on webportal, communication, translations, access to document requests and re-examinations of applicable || 193,75 || 124,1 || 40 || €961 775 || || || || ||

193,75 || 79,5 || 40 || €616 125 || || || || ||

16 || || || PRAC Staff time related to referrals || 54 || 124,1 || 11 || €73 715 || 130 || 109 || 11 || €155 870 ||

54 || 79,5 || 11 || €47 223 || || || || ||

17 || || || CHMP/CMDh Staff time related to referrals || 54 || 124,1 || 11 || €73 715 || 65 || 109 || 11 || €77 935 ||

81 || 79,5 || 11 || €70 835 || || || || ||

|| 17a || || || Evaluation/assessment within PhV Refferals || || || || || 360 || 109 || 40 || €1 569 600 ||

|| || || || Sub-total PhV Referrals || || || || €4 887 616 || || || || €1 803 405 || €6 691 021

4. Other costs
of the Agency related to pharmacovigilance

Activities || EMA || Rapporteurs / NCA || Total cost

|| || || || || Nr of hours required || Hourly rate / wage || Frequency per year || EMA total || No. of hours required || Hourly rate / wage || Frequency per year || Rapporteur total

|| 18 || Literature monitoring || Outsourced literature monitoring and entering of data in EudraVigilance || 8153 || 124,1 || 1 || €1 011 787 || || || || ||

|| 19 || Quality control of the outsourced activities and entered data || 4455 || 124,1 || 1 || €552 866 || || || || ||

|| || ICT || || IT development and software maintanace || || || || €4 882 643 || || || || ||

|| || || IT infrastructure maintanace || || || || €2 061 636 || || || || ||

|| 22 || Signal detection + ADRs handling + Risk management || || Scientific validation of product and substance data submitted by the MAHs (outsorced) || 22390 || 124,1 || 1 || €2 778 599 || || || || ||

Other || 23 || || Clinical validation of signals, signal management by scientific staff and provision of analysis from EudraVigilance database and other data sources at the request from MS || 10 197 || 124,1 || 1 ||  € 1 265 455 || || || || ||

|| 2 499 || 79,5 || 1 ||  €198 670 || || || || ||

24 || || Management of RMPs including procedural support through PRAC, monitoring the outcome of risk minimisation measures and preparation of documents for publication for CAPs and for NAPs at the request of a member state. || 17820 || 124,1 || 1 || €2 211 462 || || || || ||

|| 6534 || 79,5 || 1 || €519 453 || || || || ||

25 || || Monitoring the effectiveness of public health measures (e.g. risk management systems, through outsources studies of their outcomes using longitudinal patient databases). || 7643 || 124,1 || 1 || €948 496 || || || || ||

26 || || Coordination of pharmacovigilance inspections, information gathering on non-compliance and follow-up || 6534 || 124,1 || 1 || €810 869 || || || || ||

|| 3861 || 79,5 || 1 || €306 950 || || || || ||

27 || || Translations of communication related material and of data received from the public in relation to referrals || 3370 || 124,1 || 1 || €418 217 || || || || ||

28 || || || PRAC Staff time (remaining) || 891 || 124,1 || 1 || €110 573 || || || || ||

|| || 891 || 79,5 || 1 || €70 835 || || || || ||

29 || || || PRAC meeting costs || || || || €564 503 || 194 || 109 || 11 || €232 606* ||

30 || || || CHMP meeting costs || || || || €112 901 || || || || ||

|| || || || Sub-total other || || || || €18 825 914 || || || || €232 606 || €19 058 520

*reimbursement to PRAC members

Estimation of the overall impact of the proposed
legislation on the budget of the Agency

|| Year 2014* || Year 2015 || Year 2016 || Year 2017 || Year 2018 || Year 2019 || Year 2020

FTE ** || 0 || 38 || 38 || 38 || 38 || 38 || 38

Annual salaries** || €0 || €5 108 855 || €5 108 855 || €5 108 855 || €5 108 855 || €5 108 855 || €5 108 855

Annual cost other than personnel || €11 277 314 || €22 906 802 || €22 906 802 || €22 906 802 || €22 906 802 || €22 906 802 || €22 906 802

Rapporteurs' remuneration || €5 265 082 || €10 530 163 || €10 530 163 || €10 530 163 || €10 530 163 || €10.530.163 || €10 530 163

Total cost || €16 542 396 || €38 545 820 || €38 545 820 || €38 545 820 || €38 545 820 || €38.545.820 || €38 545 820

Income PhV Fees || €16 542 396 || €38 545 820 || €38 545 820 || €38 545 820 || €38 545 820 || €38.545.820 || €38 545 820

Balance || 0 || 0 || 0 || 0 || 0 || 0 || 0

*based on the assumption that the Regulation becomes
applicable in summer 2014

**incremental to 23 FTE as per financial statement of
the 2008 legislative proposal,
COM(2008) 664 final

The distribution by grades is as follows:

Posts || 2015 || 2016 || 2017 || 2018 || 2019 || 2020

AD12 || 1 || 1 || 1 || 1 || 1 || 1

AD9 || 4 || 4 || 4 || 4 || 4 || 4

AD8 || 9 || 9 || 9 || 9 || 9 || 9

AD6 || 13 || 13 || 13 || 13 || 13 || 13

Total AD || 27 || 27 || 27 || 27 || 27 || 27

AST3 || 7 || 7 || 7 || 7 || 7 || 7

AST1 || 4 || 4 || 4 || 4 || 4 || 4

Total AST || 11 || 11 || 11 || 11 || 11 || 11

Total posts || 38 || 38 || 38 || 38 || 38 || 38

The human resources required could be met by staff
redeployed within the Agency or additional staff under the strict condition
that sufficient posts are available within the context of the global
legislative financial statements’ revision exercise and the annual allocation
procedure for agencies, in the light of budgetary constraints which are
applicable to all EU bodies.

Agency data used for calculations of cost

1. Productive working days/year || 2012 || 2016

|| 198 || 199

2. Standard working hours/year || 2012 || 2016

Standard working hours/day || 8 * || 8 *

x number of productive days/year || 198 || 199

Total number of productive hours/year || 1 584 || 1 592

3. Average staff cost || 2012 || 2016

Average salary items AD || 138 579 || 142 655

Overhead (non-salary cost, building, equipment, support and management) || 57 991 || 51 638

Total staff cost AD || 196 570 || 194 293

Average salary items AST || 75 043 || 77 250

Overhead (non-salary cost, building, equipment, support and management) || 50 920 || 44 456

Total staff cost AST || 125 963 || 121 706

Average salary items Contract Agent || 48 538 || 53 360

Overhead (non-salary cost, building, equipment, support and management) || 47 970 || 41 833

Total staff cost Contract Agent || 96 508 || 95 193

|| ||

Notes: || 2012 || 2016

Weighting on salary items assumed (including exchange rate) || 148 || 130

Employers pension contribution included || no || yes

Source: EMA

*A working week of
40 hours is applied to all calculations.

[1]               OJ L 136, 30.4.2004.

[2]               OJ L 311, 28.11.2001.

[3]               Regulation (EU) No 1235/2010 of the European
Parliament and of the Council amending, as regards pharmacovigilance of
medicinal products for human use, Regulation (EC) No 726/2004 and Directive
2010/84/EU of the European Parliament and of the Council amending, as regards
pharmacovigilance, Directive 2001/83/EC, OJ L 348 of 31.12.2010.

[4]               Directive 2012/26/EU, OJ L 299 of 27.10.2012, and
Regulation (EU) No 1027/2012, OJ L 316 of 14.11.2012.

[5]               Report on the annual accounts of the European
Medicines Agency for the financial year 2011, together with the Agency’s
replies (2012/C 388/20), OJ C 388/116, 15.12.2012

[6]               Resolution of the European Parliament of 23 October
2012 with observations forming an integral part of its Decision on discharge in
respect of the implementation of the budget of the European Medicines Agency
for the financial year 2010, OJ L 350, 20/12/2012 p. 0082 - 0087

[7]               Registered in the database provided for in Article
57(1)(l) of the Regulation.

[8]               OJ L 35, 15.2.1995, p. 1.

[9]               OJ C , , p. .

[10]             OJ C , , p. .

[11]             OJ L 136, 30.4.2004, p. 1.

[12]             OJ L 311, 28.11.2001, p. 67.

[13]             OJ L 348, 31.12.2010, p.74.

[14]             OJ L 348, 31.12.2010, p.1.

[15]             OJ L 299, 27.10.2012, p.1.

[16]             OJ L 316, 14.11.2012, p.38.

[17]             OJ L 35, 15.2.1995, p. 1.

[18]             OJ L 124, 20.5.2003, p.36.

[19]             OJ L 257, 27.10.1995, p.1.

[20]             OJ L 35, 15.2.1995, p. 1.

[*]            Date of entry into force of the basic legislative act
or any other date set by the legislator.[To be adapted by the legislator]

[21]             ABM: Activity-Based Management – ABB: Activity-Based
Budgeting.

[22]             As referred to in Article 49(6)(a) or (b) of the
Financial Regulation.

[23]             Details of management modes and references to the
Financial Regulation may be found on the BudgWeb site: http://www.cc.cec/budg/man/budgmanag/budgmanag_en.html

[24]             As referred to in Article 185 of the Financial Regulation.

[25]             Diff. = Differentiated appropriations / Non-Diff. =
Non-differentiated appropriations.

[26]             EFTA: European Free Trade Association.

[27]             Candidate countries and, where applicable, potential
candidate countries from the Western Balkans.

[28]             Year N is the year in which implementation of the
proposal/initiative starts.

[29]             Technical and/or administrative assistance and
expenditure in support of the implementation of EU programmes and/or actions (former
'BA' lines), indirect research, direct research.

[30]             Year N is the year in which implementation of the
proposal/initiative starts.

[31]             Outputs are products and services to be supplied (e.g.:
number of student exchanges finances, number of km of roads built, etc.).

[32]             As described in point 1.4.2. 'Specific objective(s)...'.

[33]             Year N is the year in which implementation of the
proposal/initiative starts.

[34]             Technical and/or administrative assistance and
expenditure in support of the implementation of EU programmes and/or actions
(former 'BA' lines), indirect research, direct research.

[35]             CA= Contract Agent; LA = Local Agent; SNE = Seconded
National Expert; INT = agency staff ('Intérimaire'); JED = 'Jeune Expert en
Délégation' (Young Experts in Delegations).

[36]             Sub-ceiling, for external staff covered by operational
appropriations (former "BA" lines).

[37]             See points 19 and 24 of the Interinstitutional
Agreement.

[38]             As regards traditional own resources (customs duties,
sugar levies), the amounts indicated must be net amounts, i.e. gross after
deduction of 25% for collection costs.

[39]             Amounts that are used for fee levels and rapporteur
remuneration have been rounded to the nearest hundred euros. Administrative
cost is included.